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Integrating network pharmacology and Mendelian randomization to explore potential targets of matrine against ovarian
Xiaoqun Chen1, Yingliang Song2
1Department of Ultrasound, Affiliated Hospital of Shaoxing University (The Shaoxing Municipal Hospital), Shaoxing, Zhejiang, China.
Background:
Matrine has been reported inhibitory effects on ovarian cancer (OC) cell progression, development, and apoptosis. However, the molecular targets of matrine against OC and the underlying mechanisms of action remain elusive.
Objective:
This study endeavors to unveil the potential targets of matrine against OC and to explore the intricate relationships between these targets and the pathogenesis of OC.
Methods:
The effects of matrine on the OC cells (A2780 and AKOV3) viability, apoptosis, migration, and invasion was investigated through CCK-8, flow cytometry, wound healing, and Transwell analyses, respectively. Next, Matrine-related targets, OC-related genes, and ribonucleic acid (RNA) sequence data were harnessed from publicly available databases. Differentially expressed analyses, protein-protein interaction (PPI) network, and Venn diagram were involved to unravel the core targets of matrine against OC. Leveraging the GEPIA database, we further validated the expression levels of these core targets between OC cases and controls. Mendelian randomization (MR) study was implemented to delve into potential causal associations between core targets and OC. The AutoDock software was used for molecular docking, and its results were further validated using RT-qPCR in OC cell lines.
Results:
Matrine reduced the cell viability, migration, invasion and increased the cell apoptosis of A2780 and AKOV3 cells (P< 0.01). A PPI network with 578 interactions among 105 candidate targets was developed. Finally, six core targets (TP53, CCND1, STAT3, LI1B, VEGFA, and CCL2) were derived, among which five core targets (TP53, CCND1, LI1B, VEGFA, and CCL2) differential expressed in OC and control samples were further picked for MR analysis. The results revealed that CCND1 and TP53 were risk factors for OC. Molecular docking analysis demonstrated that matrine had good potential to bind to TP53, CCND1, and IL1B. Moreover, matrine reduced the expression of CCND1 and IL1B while elevating P53 expression in OC cell lines.
Conclusions:
We identified six matrine-related targets against OC, offering novel insights into the molecular mechanisms underlying the therapeutic effects of matrine against OC. These findings provide valuable guidance for developing more efficient and targeted therapeutic approaches for treating OC.
Insights
Matrine exhibits inhibitory effects on ovarian cancer (OC) by targeting key genes like TP53 and CCND1. This study identifies six core targets, offering insights into matrine
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Matrine demonstrates inhibitory effects on ovarian cancer (OC) progression and apoptosis.
- The precise molecular targets and mechanisms of matrine in OC remain largely unknown.
Purpose of the Study:
- To identify potential molecular targets of matrine against OC.
- To elucidate the relationship between these targets and OC pathogenesis.
Main Methods:
- Investigated matrine's effects on OC cell viability, apoptosis, migration, and invasion.
- Utilized bioinformatics analyses (PPI network, Venn diagrams) on public databases to identify core targets.
- Validated target expression and causal associations using GEPIA, Mendelian randomization, molecular docking, and RT-qPCR.
Main Results:
- Matrine reduced OC cell viability, migration, and invasion, while increasing apoptosis.
- Six core targets (TP53, CCND1, STAT3, IL1B, VEGFA, CCL2) were identified.
- TP53 and CCND1 were identified as risk factors for OC; matrine showed binding potential to TP53, CCND1, and IL1B, modulating their expression in OC cells.
Conclusions:
- Identified six matrine-related targets providing novel insights into its therapeutic mechanisms against OC.
- Findings guide the development of more effective and targeted therapeutic strategies for OC treatment.
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